Number Of Head Dips Research Articles

Anxiolytic-Like Effects of (O-Methyl)-N-2,6-dihydroxybenzoyl-tyramine (Riparin III) from Aniba riparia (NEES) MEZ (Lauraceae) in Mice

This work presents behavioral effects of (O-methyl)-N-2,6-dihydroxybenzoyl-tyramine (riparin III) isolated from the unripe fruit of Aniba riparia (Nees) Mez (Lauraceae) in animal models of open field, rota rod, elevated plus maze and hole board tests in mice. Riparin III (ripIII) was administered orally, in male mice, at single doses of 25 and 50 mg/kg. The results showed that ripIII, at both doses, had no effects on the spontaneous motor activity in the rota rod test nor in the number of squares crossed in the open field test. However, riparin III decreased the number of grooming and rearing. In the plus maze test, ripIII, at both doses increased the following parameters: percentage of entries in the open arms (PEOA), time of permanence in the open arms (TPOA) and percentage of time of permanence in the open arms (PTOA) and at the dose of 50 mg/kg, increased the number of entries in the open arms (NEOA). Similarly, ripIII, at both doses, showed an increase in the number of head dips into the holes of the hole board test. These results show that riparin III presents anxiolytic effects in the plus maze and hole board tests which are not influenced by the locomotor activity in the open field test.

Behavioral effects of urotensin-II centrally administered in mice

Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.

Effect of leaves of Butea frondosa on stress, anxiety, and cognition in rats

The plant Butea frondosa has been indicated in the Indian system of medicine as a plant augmenting memory and as a rejuvenator. The effect of oral administration of the aqueous and alcoholic extracts of the leaves was assessed on stress, cognitive function, and anxiety in albino rats. The antistress activity was evaluated using cold restraint induced ulcers and leukocyte count after subcutaneous injection of milk. The aqueous extract provides protection against stress-induced gastric lesions while both the alcoholic as well as the aqueous extract normalizes the white blood cell count. Effect on cognitive function was evaluated using Cook and Weidley's pole apparatus. The results indicate that the aqueous extract and the alcoholic extract when administered at a dose of 300 mg/kg for a period of 7 days augment both the acquisition as well as the retention of memory of learned task. The absence of an increase in the occupancy of the open arm in the elevated plus maze and in the number of head dips in the hole-board paradigms indicates that both the extracts are devoid of anxiolytic activity. Nootropic activity was compared using piracetam (100 mg/kg po) as the standard, while for anxiolytic and antistress activity, diazepam (1.0 mg/kg ip) was employed as the standard drug. It is concluded that the aqueous and alcoholic extract of B. frondosa possesses antistress and weak nootropic activity.

Anxiolytic-like action of orally administered dl-tetrahydropalmatine in elevated plus-maze

dl-Tetrahydropalmatine ( dl-THP), a naturally occurring alkaloid, has been intensively studied for its sedative and hypnotic effects. Putative explanation for its mechanism and target of action involves the dopaminergic neurotransmission system. In view of the close interactions between the dopaminergic and the GABAergic neurons in the amygdala, pharmacological effects of dl-THP were tested for activity at the GABA A receptor benzodiazepine site (BDS). Effects of dl-THP were examined in mice employing the elevated plus-maze, the holeboard and the horizontal-wire tests. In the elevated plus-maze, mice treated with low doses of dl-THP (0.5–10 mg/kg) exhibited significant increase in the percentage of entries and time spent in open arms without altering the number of closed-arm entries when compared to the control group, indicative of its selective anxiolytic effect. In the holeboard and horizontal wire tests, where exploratory behavior and potential muscle relaxant effect were assessed, respectively, only mice treated with as much as 50 mg/kg dl-THP manifested sedation and myorelaxation, as observed in the significant decrease in the number of head dips and the decrease in the percentage of mice grasping wire in comparison to control. Notably, coadministration of the BDS antagonist flumazenil abolished the dl-THP-induced anxiolysis as seen in the reversal of the increase of both the number of entries and time spent in open arms back to basal levels in the elevated plus-maze test. The results suggest that dl-THP at defined low dosages acts as anxiolytics in mice, and the BDS mediates, at least in part, such anxiolytic effect of dl-THP.

Seasonal peculiarities of behavior of ground squirrel Citellus undulatus in holeboard and open field tests

Seasonal changes in the behavior of ground squirrels Citellus undulatus ( n=35) in holeboard and open field tests were studied. It was found that the number of head dips and rearings in the holeboard and the number of crossed squares, rearings, and runs across the field center in the open field in ground squirrels during arousal between bouts at the end of the hibernation period, in the middle of March, were lower than these indices in active summer animals. A rapid restoration of all behavioral parameters after the arousal of animals from hibernation in mid-April was shown. In some cases, the behavioral parameters of activity in the holeboard and open field tests and the habituation reaction reached the values characteristic of active summer animals in a very short period of time, sometime within 1 day. By contrast, the locomotory and exploratory activities of animals tested in autumn (at the beginning of September and in the middle of October) were significantly lower than in summer animals, i.e. these indices decreased to minimum values 1.5–2 months prior to their entry into hibernation. The results of behavioral experiments indicate that the preparation of the CNS of hibernators for seasonal changes in the functional states is under the control of endogenous regulators.

Interference of propylene glycol with the hole-board test.

Experimental drugs and/or plant extracts are often dissolved in solvents, including propylene glycol. Nevertheless, there is evidence for psychoactive properties of this alcohol. In this study we found that in the hole-board test 10% propylene glycol did not modify the head-dipping behavior. However, 30% propylene glycol induced an increase in the number of head-dips (46.92 +/- 2.37 compared to 33.83 +/- 4.39, P<0.05, ANOVA/Student-Newman-Keuls), an effect comparable to that obtained with 0.5 mg/kg diazepam (from 33.83 +/- 4.39 to 54 +/- 3.8, P<0.01, ANOVA/Student-Newman-Keuls). These results demonstrate that 30% propylene glycol has significant anxiolytic effects in this model and therefore cannot be used as an innocuous solvent.

Differential Effects of Beta-Carbolines and Antidepressants on Rat Exploratory Activity in the Elevated Zero-Maze

PÄHKLA, R., A. KASK AND L. RÄGO. Differential effects of beta-carbolines and antidepressants on rat exploratory activity in the elevated zero-maze. PHARMACOL BIOCHEM BEHAV 65(4) 737–742, 2000.—Present experiments were designed to compare the effects of antidepressants desipramine (10 and 20 mg/kg IP) and fluoxetine (5 and 10 mg/kg IP) with anxiogenic β-carboline DMCM (0.5 and 1.0 mg/kg IP) in the elevated zero-maze test in rats. The second aim of this study was to assess the effects of pinoline (6-methoxy-1,2,3,4-tetrahydro-β-carboline) in the rat elevated zero-maze test in comparison with structurally unrelated β-carboline DMCM and antidepressants. The time spent in the open part of the elevated zero-maze was not significantly affected by antidepressants, but was decreased by β-carbolines pinoline and DMCM. The number of line crossings in the open parts and the number of head dips were also decreased more by β-carbolines in comparison with antidepressants. Latency to enter the open part was statistically significantly increased only by DMCM. Measurement of locomotor activity in a separate experiment indicated that activity of the rats' time moving, distance traveled, and number of rearings were reduced by all four drugs studied. These results demonstrate that the effects of antidepressants in the elevated zero-maze test differ from the effects of the reference anxiogenic compound DMCM. The effects of pinoline and DMCM in the zero-maze test were similar, which suggests the involvement of mechanisms other than serotoninergic in the action of pinoline.

The Effects of Cholecystokinin A and B Receptor Antagonists on Exploratory Behaviour in the Elevated zero-maze in Rat

The aim of the present study was to investigate the effects of cholecystokinin (CCK) CCK A and CCK B receptor antagonists SR 27897 B, devazepide, L 365260 and PD 135158 (CAM 1028) on exploratory behaviour in the elevated zero-maze in the rat. For further validation of the elevated zero-maze, the effects of a reference anxiolytic diazepam (0.25, 0.5, 1.0, 2.0 mg/kg), a non-benzodiazepine (BDZ) anxiolytic buspirone (0.04, 0.2, 1.0, 5.0 mg/kg), BDZ receptor inverse agonists FG 7142 (5, 10, 15,20 mg/kg) and DMCM (0.1, 0.5, 1.0, 1.5 mg/kg), and a BDZ receptor antagonist flumazenil (10 mg/kg) were studied. Diazepam decreased the number of stretched-attend postures in all doses used and increased the percentage of time spent exploring in open parts at doses of 0.5 and 1.0 mg/kg. The effects of diazepam were blocked by flumazenil. FG 7142 and DMCM had effects only in subconvulsive doses (20 mg/kg and 1.5 mg/kg). Flumazenil and buspirone failed to show any effect. The CCK A receptor antagonists were also without any effect. The CCK B receptor antagonists L 365260 (1.0 and 5.0 mg/kg) and PD 135158 (100 μg/kg) had a significant anxiolytic-like effect. The CCK B receptor antagonists increased the number of open part entries, the number of head dips, the percentage of time spent exploring in the open part and decreased the number of stretched-attend postures. These data support the hypothesis of the involvement of the CCK B receptor subtype in the neurobiological mechanisms of anxiety. © 1997 Elsevier Science Ltd. All rights reserved.

Prenatal protein malnutrition affects exploratory behavior of female rats in the elevated plus-maze test

To study the effects of prenatal protein deficiency in the exploration of the elevated plus-maze, an ethological procedure was used. Female rats were provided with 25% (control) or with 6% (low-protein) casein diets before and during pregnancy. After birth eight pups in each litter (six males and two females) were fostered to a control mother. After weaning (21 days of age) all animals received a lab chow diet until behavioral testing began at 70 days of age. Individual prenatally malnourished ( n = 12) and well-nourished ( n = 12) females were placed at the center of the elevated plus-maze and allowed to explore for a 5-min session. One session was given per day for 6 consecutive days. The following variables were recorded: percentage of open arm entries; percentage of time spent in open arms; total arm entries; time in the center platform; latency to first open arm entry; number of attempts to enter an open arm; number of rearings; number of head-dips. The results showed a significant effect of malnutrition on six behaviors (percent open arm entries, percent time spent in open arms, attempts to enter open arms, rearings, head-dips, and latency to first open arm entry) and a significant diet by session interaction on two behaviors (attempts to enter open arms and head-dips). These results indicate increased exploration of the open arms in prenatally malnourished as compared with well-nourished control rats, suggestive of lower anxiety and/or a higher impulsiveness in these animals.

Handling alters habituation and response to stimulus change in the holeboard

The responses of rats that had been extensively handled for 18 days were compared in the holeboard with those of rats that had received handling for only 4 days before the test. The extensively handled group showed slower between-day habituation of exploratory head-dipping. They did not differ in the number of head-dips, but spent longer head-dipping, at holes with objects than at those without. The less-handled group did not differ in the time spent head-dipping, but made more head-dips at empty holes. Both groups reacted similarly to the removal of the objects on day 4. However, the extensively handled rats showed a greater response of increased head-dipping when a novel object was introduced on day 5. The groups did not differ in their locomotor activity, but the extensively handled group made more rears. The results are discussed with respect to the neurochemical changes that have been found after repeated handling.

Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora Coerulea

The pharmacological effects of 5,7-dihydroxyflavone (chrysin), a naturally occurring monoflavonoid that displaces [ 3H]flunitrazepam binding to the central benzodiazepine (BDZ) receptors, were examined in mice. In the elevated plus-maze test of anxiety, diazepam (DZ, 0.3–0.6 mg/kg) or chrysin (1 mg/kg) induced increases in the number of entries into the open arms and in the time spent on the open arms, consistent with an anxiolytic action of both compounds. The effects of chrysin on the elevated plus-maze was abolished by pretreatment with the specific BDZ receptor antagonist Ro 15-1788 (3 mg/kg). In the holeboard, diazepam (1 mg/kg) and chrysin (3 mg/kg) increased the time spent head-dipping. In contrast, high doses of DZ (6 mg/kg) but not of chrysin produced a decrease in the number of head dips and in the time spent head-dipping. In the horizontal wire test, diazepam (6 mg/kg) had a myorelaxant action. In contrast, chrysin (0.6–30 mg/kg) produced no effects in this test. These data suggest that chrysin possesses anxiolytic actions without inducing sedation and muscle relaxation. We postulate that this natural monoflavonoid is a partial agonist of the central BDZ receptors.

Anxiolytic effects of nitrous oxide in mice in the light-dark and holeboard exploratory tests.

To investigate anxiolytic effects of nitrous oxide (N2O), male mice were tested in two exploratory models--a two-chambered light-dark (L-D) unit and a holeboard. Tests were conducted inside a glovebag through which one of three mixtures of N2O and oxygen (25, 50 and 75% N2O) or room air (RA) was circulated at a flow rate of 10 l/min. The principal findings in the L-D unit were a concentration-related increase in number of interdepartmental transitions and a generalized increase in time spent on the light side. Nitrous oxide effectively elevated transitions in the L-D unit at a lower concentration (25% N2O) than was required to increase locomotor activity in an open field (50% N2O), suggesting that these two measures are at least partially independent; transitions might reflect a specific exploratory component of locomotor behavior. In the holeboard test, a concentration-related increase in number of head dips was observed. Pretreatment with naltrexone-HCl or saline vehicle revealed a contribution by an endogenous opioid-linked locomotor stimulant effect in some measures. A dose-related reversal by flumazenil of 50% N2O-induced shifts in number of head dips and time spent head-dipping implicates a benzodiazepine receptor. Both paradigms, in particular the holeboard, should prove useful in future N2O research.

Influence of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test

The effects of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test were studied. When tested immediately or 24 h after 1 h exposure to noise, restraint in tubes or tail shock, no changes in either defecation rate or activity in the holeboard were observed. In contrast, immediately after 1 h immobilization in wood-boards, a reduction of the number of areas crossed and the number of head-dips was found. The inhibitory effect of immobilization on head-dips persisted 24 h later. The behavior of the rats in the forced swim test was classified into three categories: struggling, mild swim and immobility. The changes in the behavior were critically dependent on the type of stressor, and more specifically on its intensity, that was evaluated with three different physiological parameters (serum prolactin, corticosterone and glucose levels). Thus, if tested immediately after stress, noise did not alter the response of the rats, restraint in tubes and tail shock-reduced immobility, and the latter stressor increased mild swim. In the second experiment, immobilization in wood-boards reduced struggling. Twenty-four hours after stress, noise, restraint in tubes or tail shock were without effect, but immobilized rats showed increased immobility and reduced mild swim activity. The present data clearly indicate that behavior of rats in a holeboard and in a forced swim situation are not related, and that acute stress could have a differential effect on the various categories of behavior in a forced swim situation.

Effects of sodium phenobarbital on motor activity and exploration in the mouse: Development of tolerance and incidence of withdrawal responses

Sodium phenobarbital (20 mg/kg) was without significant effect on exploratory head-dipping, but a higher dose (70 mg/kg) significantly reduced the number of head-dips and the time spent head-dipping 0.5 and 8 hr after acute administration. Tolerance developed rapidly, i.e., by day 7 of treatment, to these reductions. Both doses of phenobarbital significantly increased locomotor activity, the increase was more marked for the 70 mg/kg dose and for this dose was greater 8 hr after administration than 0.5 hr. No tolerance developed over 21 days of treatment to the increase in locomotor activity 0.5 hr after drug administration; some tolerance did develop by day 14 to the increase detected 8 hr after drug administration, but this is likely to be metabolic. After 21 days of treatment, sodium phenobarbital was withdrawn. Twenty-four hours after the last dose of 70 mg/kg there was a significant reduction in the time spent head-dipping; there was also significant reduction in locomotor activity, which peaked 48 hr after the last dose.

The role of the benzodiazepine receptor in mediating long-lasting anticonvulsant effects and the late-appearing reductions in motor activity and exploration

The number of head-dips, the time spent head-dipping, the number of rears and the locomotor activity of mice placed in a holeboard was reduced by lorazepam (0.25 mg/kg) 1 and 1.5 h after oral administration and these reductions were reversed by the benzodiazepine antagonist flumazenil (1 mg/kg). Activity returned to control levels at 3 and 4.5 h for head-dipping, and between 3 and 12 h for rearing and locomotor activity. However, significant late-appearing reductions were found for the number of head-dips and the time spent head-dipping (6 h) and rearing and locomotor activity (15 h) and these decreases could not be reversed by flumazenil. Similar results were found after oral administration of oxazepam (7 mg/kg). Oxazepam reduced the number of head-dips and time spent head-dipping at 1, 1.5 and 3 h and these reductions were reversed by flumazenil (1 mg/kg). Head-dipping activity returned to normal at 4.5 h. Significant reductions were also found for both measures at 1, 6 and 7.5 h and these late reductions could not be reversed by flumazenil. This suggests that the late-appearing reductions in holeboard behaviours, resulting from lorazepam or oxazepam administration to mice, is not mediated by the benzodiazepine receptor. This conclusion was supported by the results from in vivo binding, which showed no change in the % receptor occupancy 3-15 h after administration of lorazepam or oxazepam. In contrast to the holeboard behaviours, the anticonvulsant effects of the two drugs showed good correlations with receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the effects of clonidine, rilmenidine, and guanfacine in the holeboard and elevated plus‐maze

AbstractThe effects of clonidine, rilmenidine, and guanfacine were studied in the holeboard and elevated‐plus maze tests in rats. In the holeboard test, clonidine had a profound effect on locomotor activity, significantly (P &lt; 0.05) reducing this measure at all but one of the doses tested (0.005–0.25 mg/kg). In contrast, rilmenidine and guanfacine only markedly affected locomotor activity at 2.5 mg/kg or higher. The ED50&lt;apos;s for locomotor activity were as follows: clonidine, 0.024 mg/kg; rilmenidine, 1.92 mg/kg; and guanfacine 1.65 mg/kg. All three compounds also caused significant decreases in the number of head dips and time spent head‐dipping. The effects of clonidine (0.005–0.25 mg/kg)and rilmenidine (0.25–10 mg/kg)on the number of head‐dips were significant (P &lt; 0.01) at all doses and were dose dependent. The actions of guanfacine were similar, with all doses (0.125–5 mg/kg) differing significantly (P &lt; 0.05) from the controls, except 1 mg/kg. However, the time spent head‐dipping was only decreased significantly (P &lt; 0.05) by clonidine (0.005–0.25 mg/kg), rilmenidine (1,5, and 10 mg/kg), and guanfacine (0.5–5.0 mg/kg). In the elevated plus‐maze, clonidine had no significant effect on the % number of entries made onto open arms, or the % of time spent on the open arms; rilmenidine reduced the % time spent on the open arms, but this decrease was secondary to the drop in total activity; in contrast, guanfacine reduced both the % number of entries made onto open arms and the % time spent on the open arms, and this was independent of the drop in total arm entries, thus indicating an anxiogenic‐like effect. The results show that all three compounds are sedative (as judged by reductions in locomotor activity in the holeboard), with clonidine being much more potent on this measure. Guanfacine differed from the other two compounds in its apparent anxiogenic‐like effects in the plus maze.

Behavioral interactions between ethanol and imidazodiazepines with high affinities for benzodiazepine receptors

The intrinsic effects of two imidazodiazepines RO 15–3505 and RO 17–1812 on the behavior of mice in a holeboard test were investigated. The interactions of these two drugs with ethanol were also studied. RO 15–3505 (0.75–6.0 mg/kg) failed to significantly alter either exploratory head-dipping or locomotor activity when administered alone but doses of 0.75 and 1.5 mg/kg reversed the reduction in the number of head-dips caused by ethanol (2 g/kg) and partially reveresed ethanol's locomotor stimulant action. In contrast, RO 17–1812 (0.75–6.0 mg/kg) increased locomotor activity when administered alone, and enhanced the reduction in exploration caused by ethanol. Neither RO 15–3505 nor RO 17–1812 altered blood alcohol concentrations suggesting a pharmacodynamic basis for these interactions. The results suggest that in the holeboard test the interactions of imidazodiazepines with ethanol are related to the nature of their interaction with benzodiazepine receptors, inverse agonists antagonising and agonists enhancing ethanol's effects on exploration.

The benzodiazepine receptor inverse agonists FG 7142 and RO 15-4513 both reverse some of the behavioral effects of ethanol in a holeboard test

The intrinsic effects of the benzodiazepine receptor inverse agonists RO 15-4513 and FG 7142 on the behavior of mice in a holeboard were investigated. Both drugs caused dose-related decreases in exploratory head-dipping. The highest dose of FG 7142 (40 mg/kg) also reduced locomotor activity. RO 15-4513 (1.5 and 3.0 mg/kg) and FG 7142 (10 and 20 mg/kg) reversed the reductions in the number of head-dips caused by ethanol (2 g/kg). The higher doses of these two drugs also partially reversed the locomotor stimulant action of ethanol. Animals that received ethanol in combination with either inverse agonist spent less time head-dipping than vehicle-treated controls. These data indicate that FG 7142 and RO 15-4513 can reverse, at least in part, some of the behavioral effects of ethanol. Neither drug significantly altered blood alcohol concentrations suggesting that the antagonism does not result from pharmacokinetic changes.

Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin.

Rats treated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, showed no differences compared to control rats in the number of head dips, a measure of exploratory behavior. Since a previous neurochemical investigation had demonstrated that DSP-4 rats have supersensitive alpha 2- and beta-adrenergic receptors in certain regions of the central nervous system, the behavior of these animals was also examined after the injection of clonidine, an alpha 2 agonist, and clenbuterol, a beta agonist. These drugs reduced, in a dose-dependent manner, the head-dipping of both control and DSP-4 rats. However, this effect was of greater magnitude in DSP-4 animals. Control experiments suggested that the response to clonidine and clenbuterol was mediated centrally by alpha 2 and beta receptors, respectively. Other behavioral experiments with agonists of the dopaminergic and serotoninergic systems indicated that these neurotransmitter systems were unchanged in DSP-4 animals. The results are discussed in terms of the selective action of DSP-4 and the responsiveness of DSP-4 rats to adrenergic agonists. The DSP-4-treated rat may constitute a new model of functional supersensitivity to adrenergic agonists.

Rapid development of tolerance to the sedative effects of lorazepam and triazolam in rats.

Acute administration of lorazepam (0.25 and 0.5 mg/kg) and triazolam (0.075-0.25 mg/kg) significantly reduced the locomotor activity of rats placed in a holeboard for 10 min. Acute injections of lorazepam (0.25 and 0.5 mg/kg) and triazolam (0.05-0.25 mg/kg) also significantly reduced exploration, measured by the number of head-dips and the time spent head-dipping. After 3 days of pretreatment, tolerance developed to the sedative effects of these drugs: lorazepam (0.25 mg/kg) and triazolam (0.05 and 1 mg/kg) were without significant effect, and lorazepam (0.5 mg/kg) had only the effect of half that dose given acutely. Some of this behavioural tolerance could be attributed to changes in drug metabolism, and the development of tolerance did not require continuous presence of drug in brain and plasma.